LECTURE 3 (Lupus) Flashcards
What is Systemic Lupus Erythematosus (SLE)?
An autoimmune disease mostly affecting women, especially African-Americans, developing between 15-45
IMMUNOLOGY:
Antibodies form against nuclear material in cells [key finding: anti-nuclear antibodies (ANA) in plasma] -> once ANA form, they form antibody-antigen complexes that circulate in plasma (Type III hypersensitivity reaction) -> deposits in many different tissues causing different symptoms -> activation of complement cascade cause damage [key finding: low C3/C4 levels (hypocomplementemia) + low CH50 levels]
CAUSES:
- unknown
- genetic, immune, environmental factors + viruses and UV light may play a role
Which antibodies cause Lupus?
- Anti-nuclear antibodies (ANA)
- Anti-double stranded DNA (anti-dsDNA)
- Anti-smith (anti-Sm)
What are Anti-nuclear antibodies (ANA)?
A type of antibody present in the serum of lupus patients and many other autoimmune disorders (also present in 5% of normal patients)
- Sensitive but not a specific test -> Negative test = disease is very unlikely
What are Anti-double stranded DNA (anti-dsDNA) antibodies?
Antibodies specific for Lupus and is associated with disease activity (increase during flare-ups) and renal involvement (more anti-dsDNA increases risk of glomerulonephritis)
What are Anti-smith (anti-Sm) antibodies?
Antibodies specific for Lupus that are directed against small nuclear ribonucleoproteins (snRNPs)
What are small nuclear ribonucleic proteins (snRNPs)?
- Combine with RNA transcripts forming a “spliceosome” -> removes a portion of the RNA transcript “splicing” to translate into a protein
- Antibodies against snRNPs found in lupus (anti-Sm)
Anti-smith antibodies is part of a panel of blood tests against nuclear antigens called the ______ panel
ENA panel
(Extractable Nuclear Antigens)
What is the function of Extractable Nuclear Antigens?
A panel of blood tests sent for patients who have suspected autoimmune disorders
What are the symptoms of Lupus?
- Signs of inflammation: Fever, weight loss, fatigue, lymphadenopathy
- Malar “butterfly” rash
- “Discoid” lesion (circular skin lesion usually on forearm)
- Raynaud’s phenomenon
- Oral/nasal ulcers
- Arthritis (tender, swollen joints)
- Serositis = inflammation of pleura (pain with inspiration), inflammation of pericardium (pericarditis)
- Anemia, thrombocytopenia, leukopenia due to Antibody attack of cells (TYPE II HYPERSENSITIVITY)
- Lupus Cerebritis
- Lupus Nephropathy
- Libman-Sacks (marantic) endocarditis
[symptoms are not constant - FLARES and remissions for a period of time]
Describe the Malar “butterfly” rash
- A classic lupus skin finding
- Common on sunlight exposure
Describe Raynaud’s phenomenon
A result of vasospasm of arteries supplying blood to the fingertips resulting in ischaemia
SYMPTOMS:
- White/blue fingertips
- Painful on exposure to the cold
- Fingertip ulcers
It can also be seen in other conditions either by itself or secondary to other autoimmune disorders
What is Lupus Cerebritis?
When lupus affects the brain and spinal cord
SYMPTOMS:
- Cognitive dysfunction (confusion and memory loss during flares)
- Stroke
- Seizures
What is Lupus Nephropathy?
When lupus affects the kidneys and can present as the nephritic or nephrotic syndrome (or both) and is the common cause of death in lupus
- Nephritic = most common SLE renal syndrome
- Nephrotic = not as common
[Nephritic syndrome = when inflamed glomeruli do not properly filter RBCs, Nephrotic syndrome = when glomeruli do not properly filter albumin]
What is Libman-Sacks/Marantic endocarditis?
A rare form of endocarditis that occurs in Lupus patients.
- Non-bacterial
- Due to inflammation of valves as a result of lupus
- Classically affects both sides of the mitral valve
What are Anti-phospholipid antibodies?
Antibodies against proteins in phospholipids that can occur in association with lupus (can also occur as a primary problem without having lupus)
CLINICAL CONSEQUENCES:
- “Antiphospholipid syndrome” (develop antiphospholipid antibodies that cause development of venous/arterial thrombosis -> DVT, stroke, foetal loss)
- Increased PTT
- False positive syphilis test
What are the three clinically relevant anti-phospholipid antibodies?
- Anti-cardiolipin
[antibody responsible for false positive syphilis (RPR/VDRL) test since also bind with RPR/VDRL antigens] - Lupus anticoagulant
[intereferes with PTT test by giving a false elevation] - Anti-B2 glycoprotein
How do you diagnose lupus?
You need to diagnose 4 out of 11 criteria
CRITERIA:
1. Malar rash
2. Discoid rash
3. Photosensitivity
4. Oral ulcers
5. Arthritis
6. Serositis
7. Cerebritis/CNS involvement
8. Renal disease
9. “Penias”
10. ANA
11. Another antibody test = Anti-dsDNA or Anti-Sm or anti-phospholipid
What is Drug-induced lupus?
Lupus-like syndrome after taking a drug
CLASSIC DRUGS:
- Isoniazid/INH (Tuberculosis drug)
- Hydralazine (Blood pressure drug)
- Procainamide (Anti-arythmic)
SYMPTOMS:
- Rash
- Arthritis
- Penias
- Positive ANA
COMPLICATIONS:
- Kidney or CNS involvement
KEY FEATURES:
- Anti-histone antibodies (rarely elevated in traditional lupus but elevated in drug-induced lupus)
- Resolves on stopping the drug
How is Lupus treated?
- Steroids
- Other immunosuppressants
- Avoid sunlight (many are photosensitive + can develop “Malar rash” and flares)
- Causes of death (Renal failure, Infection [many patients take immunosuppressant drugs], Coronary disease
What is Neonatal Lupus?
An autoimmune disease in which passive transfer of autoantibodies across the placenta from the mother to the fetus results in fetal and neonatal disease
- Occurs in 1-2% of babies born if mum has autoimmune disease
- Can occur in SLE and Sjögren’s syndrome
- +SSA/Ro or +SSA/La antibodies lead to condition in foetus (elevated in SLE and Sjögren’s syndrome)
SYMPTOMS: (present at birth/first few weeks of life)
- Rash (multiple red, circular lesions on face/scalp)
- Congenital complete heart block (Slow heart rate (around 50s) and does not improve with steroids -> need a pacemaker for the rest of their lives)
